Commentary: The Best Preventive Medicine May Be None At All...

The news that hormone-replacement therapy causes harm raises a disturbing larger question: What other drugs have health authorities been wrong about?

The truth is, the hormone-replacement debacle "has underlined that we don't know a lot," says Dr. Lonny Reisman, CEO of Active Health Management Inc. And ignorance could be dangerous: Many doctors harbor concerns about everything from blockbuster cholesterol-lowering drugs to painkillers.

This doesn't mean that people should empty out their medicine cabinets. Even hormone replacement therapies have their place--relieving symptoms of menopause. And other newer drugs have been proven to work, at least in short-term clinical trials. Moreover, vague risks of cancer many years hence are irrelevant to sick patients who need drugs today.

But what worries many doctors is the growing trend of healthy people taking medicines to ward off future ills. "Most drugs do have a number of effects, both good and bad," explains Dr. Stephen B. Hulley, chair of Epidemiology & Biostatistics at the University of California at San Francisco. "We should be cautious about preventive medicine treatments that last decades."

Many women who were taking hormones to prevent osteoporosis, for example, might now turn instead to blockbuster bone-building drugs, such as Merck & Co.'s Fosamax. "The problem is that these drugs are incorporated into the bone, which is right next to the bone marrow," says Jim Carlson, assistant director of pharmacy administration at the Group Health Cooperative, a Seattle health-care provider. "The question is whether they are potentially toxic to the marrow." Merck (MRK
) says a decade of clinical studies and more than 4 million patients treated show that Fosamax has no effect on bone marrow. Carlson continues to have questions.

Potential red flags wave over other long-term-use drugs. Take antidepressants. "We don't know what happens to people who are on [them] for five years," says Dr. Karen E. Lasser of Harvard University Medical School. Meanwhile, popular--and relatively new--drugs for rheumatoid arthritis work by inhibiting an immune-system protein called tumor necrosis factor. But messing with the immune system could have unintended consequences, doctors warn.

One huge success story has been a class of drugs called statins, including Pfizer Inc.'s blockbuster, Lipitor. Statins not only lower cholesterol but have also been proved to reduce the risk of heart attacks and stroke. But in rodents, the drugs cause cancer. "The biggest question with the statins is what happens if you have been on them for 20 or 30 years. Nobody knows that--and the animal data are a cause for concern for younger people," says Dr. Thomas B. Newman, professor of epidemiology and pediatrics at UCSF. Pfizer (PFE
) says the benefits outweigh this theoretical risk.

Another popular class of drugs--acid-reducing medicines such as AstraZeneca PLC's Prilosec--can increase levels of a hormone called gastrin, which has been linked with a higher risk of cancer. AstraZeneca (AZN
) says that studies up to 12 years long show no evidence of cancer. But Dr. M. Michael Wolfe, chief of gastroenterology at Boston University School of Medicine, is not convinced. "The issue needs to be examined," he says.

Indeed, the list of issues is almost as long as the list of drugs. Do the blockbuster painkillers Vioxx and Celebrex cause heart problems? The jury is still out. Do blood-pressure-lowering calcium-channel blockers do more harm than good? Possibly. And such worries will increase as doctors try to prevent cancer with drugs. If otherwise healthy people are treated for many years, "who knows what side effects will come up?" asks Dr. Bert Vogelstein, an oncologist at Johns Hopkins University.

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The only definitive answers about safety come from big, expensive trials, such as the hormone study that sparked the latest concerns. Yet drug companies will almost never do such studies. By the time a trial arrived at an answer, the drug in question would be long off patent, and the company couldn't benefit from a good result. And government agencies have typically undertaken such research only in response to emotional debates and political pressure.

It's clear that more large studies need to be done. And drugmakers and regulators must do a far better job of spotting problems with drugs than the current flawed system. A far more rigorous system might provide hints of where larger studies are needed. Until then, Americans should take the hormone debacle to heart, and approach their medicine cabinets with a proper measure of caution.